The candidate for the K23 Award possesses a background in both Internal Medicine and Clinical Genetics. His primary career goal is to develop the requisite skills to successfully pursue independent clinical investigation in the area of adult genetic disorders. A thoughtfully designed career development plan encompassing formal training in clinical investigation, human genetics, computer database design, and medical ethics is outlined in this application. Complementing this aspect of the proposal is a research plan examining the genetic contributions to idiopathic dilated cardiomyopathy (IDC). IDC is an important and common cause of congestive heart failure. Furthermore, a substantial proportion of IDC cases (35-58%) are the result of single gene mutations; nine such genes have been linked to the disease. However, the relative contributions of each gene to the overall prevalence and phenotype of IDC are currently unknown. Such information is critical to improving the clinical diagnosis, genetic counseling, and practical management of IDC. The research proposed will elucidate the genetic epidemiology of mutations in the known relevant genes and will characterize the genotype-to-phenotype correlations that exist in both familial and sporadic cases of IDC. The approach is founded upon an existing comprehensive database that contains clinical, pedigree, laboratory, and DNA data for over 90 families. High-throughput mutation screening for mutations in described genes will be performed on the database DNA to expose the genetic epidemiology. Skills acquired in the career development phase of the award will permit further refinement of this computer database. The mutation data will be merged with the comprehensive clinical information stored in the database to uncover relationships between genotype and clinical phenotype. The research will be performed at the University of Colorado under the mentorship of Dr. Luisa Mestroni, who is a faculty cardiologist with extensive research experience and numerous publications in this field. In addition, a diverse collection of consultants has been assembled to provide ongoing expertise that is sensitive to the needs of both the research and career development plans of the candidate.